Chapter 1. Neurocircuitry of Addiction
George F. Koob, Nora D. Volkow
Abstract
Substance and alcohol use disorders cause an enormous amount of human suffering, loss of productivity, costs to our medical care system, and costs to the economy. This chapter provides a heuristic conceptual framework for alcohol and other substance use disorders, in which we integrate preclinical and clinical advances in the neuroscience of addiction that are pertinent to the prevention and management of these disorders. Conceptualization of addiction as a three-component cycle consisting of a binge/intoxication stage, a withdrawal/negative affect stage, and a preoccupation/anticipation (craving) stage has allowed identification of key neurocircuits that underlie addiction to alcohol and many other drugs. Each stage of the addiction cycle is hypothesized to represent a different domain of dysfunction that is mediated by a different neurobiological circuit. The binge/intoxication stage involves recruitment of reward neurotransmission in the basal ganglia to drive incentive salience and pathological habits. The withdrawal/negative affect stage involves loss of reward neurotransmission and gain of stress neurotransmission in the extended amygdala to drive the negative emotional state of withdrawal. The preoccupation/anticipation stage involves dysregulation of the prefrontal cortex to drive abnormal executive function and craving. Molecular genetic mediation and epigenetic loads on these same three major neurocircuits are hypothesized to confer environment-dependent and environment-independent vulnerabilities to addiction and thus represent promising targets for the development of novel approaches to strengthen resilience and prevent relapse. Accumulating data show how existing treatments for addiction work on these neurocircuits, and the growing knowledge base on the neurocircuitry of addiction provides evidence-supported information for the development of novel, science-based approaches to diagnosis, prevention, and treatment. Such advances will facilitate implementation of evidence-based practices in primary care, mental health care, and other health care settings.